Transcranial focused ultrasound (tFUS) is a novel noninvasive method of focusing energy through the skull that often uses Magnetic Resonance Imaging (MRI) for target identification, treatment planning, and closed-loop control of energy deposition[1]}. Focused ultrasound is clinically approved for thermally ablating the thalamus[2]} and when used at lower energy levels is being explored for other applications, such as drug delivery and neuromodulation[3]}. Precise focusing is critical for all tFUS procedures to minimize treatment of off-target tissues[4]}. Prior to tFUS, CT images are acquired to estimate regional skull density, speed of sound, and ultrasound attenuation during ultrasound wave propagation[5]}. Thermally ablative thalamotomy procedures use MR thermometry[6]} to intraoperatively monitor thermal dose and targeting accuracy. MR Thermometry relies on the temperature dependence of the proton resonance frequency shift to linearly map phase differences between two time points to temperature change. Another tFUS application is neuromodulation, a nonthermal method that has been demonstrated in humans targeting the thalamus[7]}, somatosensory cortex[8]}, and primary visual cortex[9]}. During neuromodulation procedures, neuronavigation aids in real-time transducer placement by calculating the position and rotation of optically tracked tools and projecting the transducer's focus onto pre-acquired images. The projected focus from optical tracking is usually a free-field estimate of the focus location[10]}, neglecting the inhomogenous layers of the skull known to shift and distort the focus[11]}. The inclusion of CT images to the neuromodulation planning process allows incorporation of skull models to map the skull layers to acoustic properties and estimate spatial accuracy, spatial extent, and output pressure for patient-specific skull models. CT imaging burdens patients by requiring longer screening time and increased risk due to radiation. For tFUS research in development and preclincal phases, it is unrealistic to obtain CT scans of a healthy participant. Therefore, it is desirable to replace the real CT (rCT) images with synthetic CT (sCT) images that are generated from other imaging modalities.
